Aspects of hormonal regulation of hepatic carbohydrate and lipid metabolism

Abstract

The liver is a major site in the rat for conversion of dietary carbohydrate
into glycogen and triglyceride. Hepatic rates of fatty acid and
glycogen synthesis were measured y vivo in response to meal-feeding
(2h/day) by the incorporation of from 3H20. This technique has not
been applied previously to glycogen synthesis and was validated in control
and streptozotocin diabetic rats* Hepatic glycogen recycling was low in
fed adult rats but was apparently greater in foetal rats. The precursor
source for glycogen synthesis in vivo could not be determined from the
distribution pattern of 3H incorporation. Hepatic glycogen synthesis was
elevated in control rats for 5h after feeding. During this phase,
glycogen could not have been a net precursor for other synthetic pathways®

Hepatic fatty acid synthesis in control rats increased 20-fold 2h after
feeding. This response was impaired and delayed, but not abolished, by
streptozotocin diabetes (55mg/kg). Insulin pretreatment (30 P.Z.I.)
restored the low diabetic rate of lipogenesis to normal by 8h after
feeding. Streptozotocin reduced the hepatic Vmax activities of glucokinase,
ATP-citrate lyase and total acetyl CoA carboxylase. None of these
enzyme activities increased when hepatic fatty acid synthesis was stimulated
by feeding in control rats or by feeding and insulin in diabetic
rats. Feeding stimulated active acetyl CoA carboxylase in control, but
not diabetic, rats. The regulation of hepatic fatty acid synthesis by
both acetyl CoA carboxylase and increased substrate concentration is
discussed.

In control rats for the first 5h after feeding, hepatic glycogen could
not have been a net fatty acid precursor. Thus the inhibition of hepatic
fatty acid synthesis in this period by glucagon (Img/kg) could not have
been directly due to depletion of glycogen® The glucagon inhibition of
lipogenesis was abolished by adrenalectomy but not potentiated by
corticotropin-treatment, suggesting a permissive role for glucocorticoid
hormones. Adrenalectomy also impaired the inhibition of hepatic pyruvate
kinase by glucagon but did not abolish the inactivation of pyruvate
kinase by 10 )jM-cyclic AMP in vitro« The involvement of L-type pyruvate
kinase in the regulation of hepatic fatty acid synthesis is discussed.
The integrated regulation of the hepatic pathways of lipogenesis,
glycolysis, gluconeogenesis and ketogenesis is considered.

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ORCID for Anthony Douglas Postle: orcid.org/0000-0001-7361-0756

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